NFNF4012

FARMAKOTERAPI DALAM ONKOLOGI DAN HEMATOLOGI

SEMESTER I
SESSION 2019-2020

TITLE : Anticancer Health Supplements

DATE : 23th November 2019
LECTURER : Assoc. Prof. Dr. Jamia Azdina Jamal

AMIRAH BINTI ABU BAKAR A158469

NURSHURNAA NISA BINTI AHMAD NIZAM A158504
NURAFIKAH BINTI SAPTU A158319
VINEETHAA A/P MARIAPPEN A158501

FACULTY OF PHARMACY
UNIVERSITI KEBANGSAAN MALAYSIA
 Figure 1.0 Bromelin

The advertisement above is a product which claimed to have anticancer effect. This product,
Brom-Q (Bromelin), claimed containing Bromelain extract. This advertisement can be easily
found in Google, Shopee or Lazada website (online shopping platform in Malaysia) with
“traditional/natural treatment for cancer” as keywords. This product claimed containing rich
content of bromelain enzymes that contributes to the effectiveness and smoothness of killing
of cancer cells towards action opens a protective coating that protects cancer cells. The
product name, Brom-Q capsules is registered under NPRA with registration number
MAL13115078T.

Bromelain enzyme in Ananas comosus extract is the active ingredient claimed to have as
anti-cancer properties in this product. The crude aqueous extract from stem and fruit of
pineapple, bromelain is a mixture of different thiol endopeptidases and other components like
phosphatases, glucosidase, peroxidases, cellulases, glycoproteins, carbohydrates, and several
protease inhibitors. The human intestines can absorb bromelain without degradation or loss of
its biological properties. Several studies showed that bromelain can inhibit cell growth and
induce cell apoptosis in different cancers through different pathways. The mechanism by
which bromelain works against cancer is not fully known. The anti-cancerous activity of
bromelain is due to its direct impact on cancer cells and their microenvironment, as well as on
the modulation of immune, inflammatory, and haemostatic systems. Bromelain is found to
increase the expression of p53 which is the well-known activators of apoptosis. It also
decreases the activity of cell survival regulators such as Akt and Erk, thus promoting
apoptotic cell death in tumours. Besides, studies showed that inhibiting NF-κB, Cox-2, and
PGE2 activity has potential effect in treatment of cancer. Bromelain found to downregulate
the NF-κB and Cox-2 expression in mouse papillomas and models of skin tumourigenesis.
Bromelain was also shown to inhibit bacterial endotoxin (LPS)-induced NF-κB activity as
well as the expression of PGE2 and COX-2 in human monocytic leukemia and murine
microglial cell lines. These pathways claim to have anticancer effects on the consumers.

Bromelain, is a proteolytic enzyme derived from pineapple (Ananas cosmosus)

recognized as anti-inflammatory, antithrombotic, fibrinolytic properties and may have
anticancer properties (Rathnavelu et al. 2016). In vitro studies suggest that Bromelain have
antiproliferative activity on different type of cancer cells in dose-dependent manner (Chang et
al. 2019; Raeisi et al. 2019). While in-vivo studies suggest that Bromelain have some capacity
for tumour shrinkage and may act synergistically with other anticancer agents (Amini et al.
2015; Debnath et al. 2019; Mohamad et al. 2019). However, the scientific evidence is still not
sufficiently supporting the use of Bromelain as an anti-cancer in human studies.

The earliest documented oral use of bromelain in breast and ovarian cancer indicates that
administration of 600 mg of bromelain/day for 6 months to several years, results in resolution
of cancerous masses and a decrease in metastasis. Further, tumour regression has been
observed when bromelain in doses above 1,000 mg daily has been combined with
chemotherapeutic agents such as 5-FU and vincristine. Orally applied bromelain stimulates
the deficient monocytic cytotoxicity of mammary tumour patients, which may partially
explain its proposed antitumor activity via the immunomodulation pathway (Eckert et al.
1999; Maurer 2001; Pillai et al. 2013). Even if Bromelain extract managed to be fully
recognized as an active ingredient with anti-cancer properties, further research needs to be
conducted to find a suitable formulation for this extract prior for the product to be used as a
cancer treatment (Zhou et al. 2017).

Besides that, this product was found to claim several medical conditions that prohibited
to be advertised. It was claimed to act as anticoagulant, anti-inflammatory, gout and arthritis.
These statement not only can lead to misconception of the function as dietary supplement, but
may worsen the condition if consumer has been taking any critical medications together with
bromelain. A previous study that conducted to assess the efficacy of bromelain in treating
osteoarthritis (OA) was reported that bromelain is not efficacious as an adjunctive treatment
of moderate to severe OA (Brien et al. 2006). Apart from that, National Center for
Complementary and Integrative Health (NCCIH) stated that there is not enough evidence to
determine if bromelain is effective for the other conditions for which it has been used,
including cancer In our opinion, the product claim was misleading and encouraging people to
buy. According to Medicines (Advertisement and Sale) Act 1956, it is clearly prohibited to
advertise this such product as the advertisement contains claim to treat cancer. Therefore, the
law must be enforced strict fully to prevent this product from confusing people especially
those cancer patients that desperate to find cure for their cancer.
In conclusion, Bromelain is a dietary supplement that can be beneficial in improving our
health but it should be taken wisely. There is lack of evidence that supported Bromelain was
indicated as anti-cancer drug and other conditions as claimed in the advertisement. In
addition, not only such product may not as effective as it’s claimed, which just burden the cost
to the user, the safety profile of this product also is questionable, thus could bring risk to the
users
References:
Amini, A., Masoumi-Moghaddam, S., Ehteda, A., Liauw, W., Akhter, J., Pilai, K. & Morris,
D. L. 2015. Abstract Lb-007: Synergistic Inhibition of Human Gastric and Colorectal
Cancers by Bromelain and N-Acetylcysteine: An in Vivo Study. Cancer Research
75(15 Supplement): LB-007.

Brien, S., Lewith, G., Walker, A., Middleton, R., Prescott, P. & Bundy, R. 2006. Bromelain as
an Adjunctive Treatment for Moderate-to-Severe Osteoarthritis of the Knee: A
Randomized Placebo-Controlled Pilot Study. Journal of the Association of Physicians
99(12): 841-850.

Chang, T. C., Wei, P. L., Makondi, P. T., Chen, W. T., Huang, C. Y. & Chang, Y. J. 2019.
Bromelain Inhibits the Ability of Colorectal Cancer Cells to Proliferate Via Activation
of Ros Production and Autophagy. PLoS One 14(1): e0210274.

Debnath, R., Majumder, D., Nath, P., Ghosh, D. & Maiti, D. 2019. Bromelain Plus Peroxidase
Reduces Non-Hodgkin Lymphoma Progression in Invivo Via up-Regulation of
Antioxidant Enzymes and Modulating Apoptotic Protein Expression. Nutrition and
Cancer 1-11.

Mohamad, N. E., Abu, N., Yeap, S. K. & Alitheen, N. B. 2019. Bromelain Enhances the Anti-
Tumor Effects of Cisplatin on 4t1 Breast Tumor Model in Vivo.
18(1534735419880258.

National Center for Complementary and Integrative Health (NCCIH) : Bromelain 2016
Retrieved from https://nccih.nih.gov/

QUEST 3+, Product Search, National Pharmaceutical Regulatory Agency, Ministry of Health
Malaysia.

Raeisi, F., Raeisi, E., Heidarian, E., Shahbazi-Gahroui, D. & Lemoigne, Y. 2019. Bromelain
Inhibitory Effect on Colony Formation: An in Vitro Study on Human Ags, Pc3, and
Mcf7 Cancer Cells. Journal of medical signals and sensors 9(4): 267-273.

Rathnavelu, V., Alitheen, N. B., Sohila, S., Kanagesan, S. & Ramesh, R. 2016. Potential Role
of Bromelain in Clinical and Therapeutic Applications. Biomedical reports 5(3): 283-
288.

Zhou, D., Porter, W. R. & Zhang, G. G. Z. 2017. Drug Stability and Degradation Studies.
Dlm. (pnyt.). Developing Solid Oral Dosage Forms, hlm. 113-149.

Amini, A., Masoumi-Moghaddam, S., Ehteda, A., Liauw, W., Akhter, J., Pilai, K. & Morris,
D. L. 2015. Abstract Lb-007: Synergistic Inhibition of Human Gastric and Colorectal
Cancers by Bromelain and N-Acetylcysteine: An in Vivo Study. Cancer Research
75(15 Supplement): LB-007.
Chang, T. C., Wei, P. L., Makondi, P. T., Chen, W. T., Huang, C. Y. & Chang, Y. J. 2019.
Bromelain Inhibits the Ability of Colorectal Cancer Cells to Proliferate Via Activation
of Ros Production and Autophagy. PLoS One 14(1): e0210274.

Debnath, R., Majumder, D., Nath, P., Ghosh, D. & Maiti, D. 2019. Bromelain Plus Peroxidase
Reduces Non-Hodgkin Lymphoma Progression in Invivo Via up-Regulation of
Antioxidant Enzymes and Modulating Apoptotic Protein Expression. Nutrition and
Cancer 1-11.

Eckert, K., Grabowska, E., Stange, R., Schneider, U., Eschmann, K. & Maurer, H. R. 1999.
Effects of Oral Bromelain Administration on the Impaired Immunocytotoxicity of
Mononuclear Cells from Mammary Tumor Patients. Oncol Rep 6(6): 1191-1199.

Maurer, H. R. 2001. Bromelain: Biochemistry, Pharmacology and Medical Use. Cell Mol Life
Sci 58(9): 1234-1245.

Mohamad, N. E., Abu, N., Yeap, S. K. & Alitheen, N. B. 2019. Bromelain Enhances the Anti-
Tumor Effects of Cisplatin on 4t1 Breast Tumor Model in Vivo.
18(1534735419880258.

Pillai, K., Akhter, J., Chua, T. C. & Morris, D. L. 2013. Anticancer Property of Bromelain
with Therapeutic Potential in Malignant Peritoneal Mesothelioma. Cancer Invest
31(4): 241-250.

Raeisi, F., Raeisi, E., Heidarian, E., Shahbazi-Gahroui, D. & Lemoigne, Y. 2019. Bromelain
Inhibitory Effect on Colony Formation: An in Vitro Study on Human Ags, Pc3, and
Mcf7 Cancer Cells. Journal of medical signals and sensors 9(4): 267-273.

Rathnavelu, V., Alitheen, N. B., Sohila, S., Kanagesan, S. & Ramesh, R. 2016. Potential Role
of Bromelain in Clinical and Therapeutic Applications. Biomedical reports 5(3): 283-
288.

Zhou, D., Porter, W. R. & Zhang, G. G. Z. 2017. Drug Stability and Degradation Studies.
Dlm. (pnyt.). Developing Solid Oral Dosage Forms, hlm. 113-149.