Cytotoxicity and genotoxicity of Hevea brasiliensis latex C-serum DCS sub-fraction as anticancer agents
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ORIGINAL PAPER
Cytotoxicity and genotoxicity of Hevea brasiliensis latex C‑serum DCS sub‑fraction as anticancer agents Yang Kok Lee1 · Ong Ming Thong2 · E. Sunderasan3 · Abd. Rahman Norazreen3 · Subramaniam Sreeramanan1,4 Received: 22 June 2020 / Accepted: 8 September 2020 © The Malaysian Rubber Board 2020
Abstract Dialysed latex C-serum supernatant (DCS) sub-fraction from the rubber tree (Hevea brasiliensis) was reported to exert significant anti-proliferative effect on specific cancer cell lines, especially in human triple negative breast cancer (MDAMB-231) and human liver carcinoma (HepG2) cells. In the present study, two human non-cancer origin cell lines, MCF-10A (human breast epithelial cells) and HDFa (human adult dermal fibroblast cells), showed least susceptibility when treated with DCS sub-fraction at concentration range 0–100 µg/mL using 2,5-diphenyl tetrazolium bromide (MTT) assay. Genotoxicity of DCS sub-fraction was assessed through Ames test, in vitro mouse lymphoma assay, and in vitro micronucleus assay. All genotoxicity experiments were tested with the presence and absence of S9 mixture as metabolic activation system. Ames test results showed negative result of mutagenicity as no clear dose-dependent relationship was observed despite mutagenic potential was detected in frame shift-based TA98 and TA1535 Salmonella typhimurium strains. Mouse lymphoma assay produced non-linear dose-dependent effect in experiments without the presence of S9. Meanwhile, experiment with the presence of S9 resulted in an inverse effect of the dose-dependent relationship. In micronucleus assay, the dose-dependent cytotoxicity effect of DCS sub-fraction showed no correlation with the increase number of cells containing micronuclei but appeared to be time-dependent. In conclusion, DCS sub-fraction showed no significant positive results in genotoxicity assays. In vivo genotoxicity assays should be conducted to ensure the safe use of DCS sub-fraction in further exploration for biological applications. Keywords Latex C-serum · Hevea brasiliensis · Cytotoxicity · Genotoxicity
Introduction
* Ong Ming Thong [email protected] * Subramaniam Sreeramanan [email protected]; [email protected] Yang Kok Lee [email protected] 1
School of Biological Sciences, Universiti Sains Malaysia, 11800 Georgetown, Penang, Malaysia
2
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Georgetown, Penang, Malaysia
3
Rubber Research Institute Malaysia (RRIM), 47000 Sungai Buloh, Malaysia
4
Centre for Chemical Biology, Universiti Sains Malaysia, Bayan Lepas, Penang, Malaysia
Hevea brasiliensis was known for high-quality latex production and timber production which was mainly used in manufacture of furniture. Decades ago, latex of the Hevea brasiliensis which appeared as the milky cytoplasm of highly specialized articulated cells, known as laticifers [1–3] was being exploited extensively. Freshly collected latex divides into three main fractions after centrifugation, where the uppermost layer know
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