Natural Product Research

Formerly Natural Product Letters

ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20

Raspberry seeds extract selectively inhibits the

growth of human lung cancer cells in vitro

Mladen Simonovic, Vesna Kojic, Dimitar Jakimov, Miodrag Glumac & Boris
Pejin

To cite this article: Mladen Simonovic, Vesna Kojic, Dimitar Jakimov, Miodrag Glumac & Boris
Pejin (2019): Raspberry seeds extract selectively inhibits the growth of human lung cancer cells in
vitro, Natural Product Research, DOI: 10.1080/14786419.2019.1666391

To link to this article: https://doi.org/10.1080/14786419.2019.1666391

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Published online: 17 Sep 2019.

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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2019.1666391

SHORT COMMUNICATION

Raspberry seeds extract selectively inhibits the growth of

human lung cancer cells in vitro
Mladen Simonovica, Vesna Kojicb, Dimitar Jakimovb, Miodrag Glumacc and
Boris Pejind
a
Institute of General and Physical Chemistry – IOFH, Belgrade, Serbia; bFaculty of Medicine,
Oncology Institute of Vojvodina, University of Novi Sad, Sremska Kamenica, Serbia; cSchool of Food
Science and Biotechnology – SFSB, Food Oral Processing Laboratory, Zhejiang Gongshang University,
Hangzhou, People’s Republic of China; dDepartment of Life Sciences, Institute for Multidisciplinary
Research – IMSI, University of Belgrade, Belgrade, Serbia

ABSTRACT ARTICLE HISTORY

This study was focused on in vitro cytotoxicity screening of the Received 2 August 2019
raspberry seeds methanol extract towards a number of cancer cell Accepted 29 August 2019
lines of human origin. The tested extract at the preferred concen-
trations (IC50 <30 mg/mL) inhibited only the growth of the lung KEYWORDS
cancer A-549 cells (IC50 ¼ 14.07 ± 0.96 mg/mL). At the same time, Soft fruit; extract; phenolics;
A-549 cells; MRC-5 cells;
it was practically inactive (IC50 >300 mg/mL) and non-mutagenic comet assay; ROS
towards normal MRC-5 lung cells. Finally, the extract potently
scavenged both OH (IC50 ¼ 20.11 ± 1.77 mg/mL) and O2- (IC50 ¼
47.23 ± 3.82 mg/mL), the free radicals of proved relevance for can-
cer pathophysiology. Though seeds were enriched with phenolic
compounds (TPC ¼ 5.21 ± 0.07 mg GAE/g), anthocyanins were pre-
sent in traces only (TAC ¼ 0.07 ± 0.003 mg cyn-3-glu/g), while
flavonoids were not detected at all. This is the first report on anti-
lung cancer potential of the seeds of any soft fruit.

1. Introduction
Wild plants, fungi and fruits are attractive due to their bioactive compounds (Pejin,
Iodice, et al. 2012; Pejin, Sabovljevic, et al. 2012; Ono et al. 2016; So et al. 2019; Zuo

CONTACT Boris Pejin brspjn@gmail.com; borispejin@imsi.rs; Mladen Simonovic mladensimonovic@gmail.com

Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1666391.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 M. SIMONOVIC ET AL.

et al. 2019). Some of them are edible, while the other can be used as medicines (Xia
et al. 2011; Pejin, Bianco, et al. 2012). Antioxidant effects are by far the most studied
ones (Giampieri et al. 2013; Karadeniz et al. 2015; Pereira et al. 2015; Radenkovs and
Feldmane 2017; Saani et al. 2018). Indeed, phenolic compounds (with stress on poly-
phenolics) are usually claimed to be responsible for these effects (Dimitri
c Markovi
c
et al. 2017; Glumac et al. 2017; Toul et al. 2017; Frezza et al. 2018; Ma et al. 2018).
Although synthetic antioxidants have been widely used in the food industry to pro-
long the shelf life, some of them such as butylated hydroxytoluene and butylated
hydroxyanisole are indeed harmful due to their likely toxicity and carcinogenicity
(Kornienko et al. 2019). As a consequence, natural antioxidants are expected to be a
good alternative to synthetic ones. Raspberries are edible fruits belonging to different
plant species from the Rubus genus. As a rich source of antioxidants, they are known
for protecting the body from cancerous growth (He et al. 2018). By the way, Serbia
managed to supply 11.85% (equal to 68.5 thousand tons) of their total world produc-
tion in 2013 (IRO 2019). This study aimed to enrich the knowledge on the biological
activity (cytotoxicity and mutagenicity) and chemical composition of the raspberry
seeds of Willamette cultivar representing 90% of the raspberries varieties widespread
in Serbia. Actually, the emphasis was on the raspberry seeds as a likely ubiquitous
resource of naturally occurring phenolics rather neglected compared both to the
whole raspberry fruits and leaves.

2. Results and discussion

According to National Cancer Institute guidelines, the crude extract with an
IC50 < 30 lg/mL is considered active (Suffiness and Pezzuto 1990). At the preferred
concentrations (IC50 <30 mg/mL), the methanol extract of the raspberry seeds of
Willamette cultivar did inhibit growth of the lung cancer A-549 cells only
(Supplementary Table S1). More precisely, IC50 values for all other cancer cell lines
(colon HT-29, HCT-116, SW-620; melanoma Hs-294T and prostate PC-3) were >100 mg/
mL. Additionally, the extract was inactive towards the normal MRC-5 cells (IC50 >300
mg/mL). However, it practically displayed no mutagenic activity in the comet assay,
unlike doxorobucin, a drug widely used in clinical practice (Supplementary Table S2).
Rather high antiradical activities towards physiologically relevant free radicals (OH and
O2-), well known for their link with cancer pathophysiology if overproduced, have
actually underpinned the assumption of their likely contribution to the observed cyto-
toxicity (Supplementary Table S3). Finally, raspberry seeds were found to be enriched
with phenolic compounds (TPC ¼ 5.21 ± 0.07 mg GAE/g). In spite of such a fact, antho-
cyanins were present in traces only (TAC ¼ 0.07 ± 0.003 mg cyn-3-glu/g), while flavo-
noids were not detected at all. A very good match between selected biological
material to be screened (in terms of TPC, Supplementary Table S4) and bioactivity has
actually lead to the sound experimental data. Compared to the acetone extract of the
freshwater sponge Ochridaspongia rotunda, the methanol extract of the raspberry
seeds was almost 3-fold less active against A-549 cells (Talevska et al. 2018). Though
sponges (both freshwater and marine) may be considered as particularly important
natural sources of cytotoxic compounds (Pejin et al. 2014), the synergistic activity of
 NATURAL PRODUCT RESEARCH 3

chemical ingredients from more common resources such as berry fruits should not be
underestimated. Polyphenolic extracts both from red and white wines were found to
exhibit some anticancer potential (Mati
c et al. 2010). If edible, such ordinary (common)
natural resources may much more easily provide the launching of new food supple-
ments with health-promoting effects on the global market.

3. Experimental
See Supplementary material.

4. Conclusion
This is one of very rare research reports dealing with cytotoxic potential of soft fruit
seeds and the first one for anti-lung cancer activity, according to the best of our
knowledge. Further research work will be directed towards comprehensive determin-
ation of the extract phenolic/polyphenolic profiles including their tentative identifica-
tion by mass spectra of higher orders.

Disclosure statement
No potential conflict of interest was reported by the authors.

Funding
This study was kindly supported by the Ministry of Education, Science and Technological
Development of the Republic of Serbia [Res. grants Nos. 31093 and 172053].

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