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Monday, 5 June 2017

Cannabidiol rather than Cannabis sativa extracts inhibit cell growth and induce apoptosis in cervical cancer cells


  • Sindiswa T. Lukhele and
  • Lesetja R. MotadiEmail author
BMC Complementary and Alternative MedicineBMC series – open, inclusive and trusted201616:335
DOI: 10.1186/s12906-016-1280-0
Received: 2 June 2016
Accepted: 11 August 2016
Published: 1 September 2016

Abstract

Background

Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies. In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.

Methods

To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted.

Results

Results obtained indicate that both cannabidiol and Cannabis sativa extracts were able to halt cell proliferation in all cell lines at varying concentrations. They further revealed that apoptosis was induced by cannabidiol as shown by increased subG0/G1 and apoptosis through annexin V. Apoptosis was confirmed by overexpression of p53, caspase 3 and bax. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels.

Conclusions

In conclusion, these data suggest that cannabidiol rather than Cannabis sativa crude extracts prevent cell growth and induce cell death in cervical cancer cell lines.

Keywords

Apoptosis Cervical cancer Cannabidiol Cannabis sativa

Background

Cannabis sativa is a dioecious plant that belongs to the Cannabaceae family and it originates from Central and Eastern Asia [1128]. It is widely distributed in countries including Morocco, South Africa, United States of America, Brazil, India, and parts of Europe [1428]. Cannabis sativa grows annually in tropical and warm regions around the world [11]. Different ethnic groups around the world use Cannabis sativa for smoking, preparing concoctions to treat diseases, and for various cultural purposes [17]. According to [28], it is composed of chemical constituents including cannabinoids, nitrogenous compounds, flavonoid glycosides, steroids, terpenes, hydrocarbons, non-cannabinoid phenols, vitamins, amino acids, proteins, sugars and other related compounds. Cannabinoids are a family of naturally occurring compounds highly abundant in Cannabis sativa plant [161424]. Screening of Cannabis sativa has led to isolation of at least 66 types of cannabinoid compounds [11430]. These compounds are almost structurally similar or possess identical pharmacological activities and offer various potential applications including the ability to inhibit cell growth, proliferation and inflammation [22]. One such compound is cannabidiol (CBD), which is among the top three most widely studied compounds, following delta-9-tetrahydrocannabinol (Δ9-THC) [14]. It has been found to be effective against a variety of disorders including neurodegerative disorders, autoimmune diseases, and cancer [2425]. In a research study conducted by [26], it was found that CBD inhibited cell proliferation and induces apoptosis in a series of human breast cancer cell lines including MCF-10A, MDA-MB-231, MCF-7, SK-BR- 3, and ZR-7-1 and further studies found it to possess similar characteristics in PC-3 prostate cancer cell line [25]. However, to allow us to further our studies in clinical trials a range of cancers in vitro should be tested to give us a clear mechanism before we can proceed. Cannabis sativa in particular cannabidiol, we propose it plays important role in helping the body fight cancer through inhibition of pain and cell growth. Therefore, the aim of this study was to evaluate the cytotoxic and anti-proliferative properties of Cannabis sativa and its isolate, cannabidiol in cervical cancer cell lines.