95 Jurnal Sains Kesihatan Malaysia Isu Khas 2018: 95-103 DOI : http://dx.doi.org./10.17576/JSKM-2018-14 Assessment of Cytotoxicity Potency of Paclitaxel in Combination with Clinacanthus Nutans Extracts on Human MDA-MB-231 Breast Cancer Cells (Penilaian Potensi Sitotoksisiti Paclitaxel secara Kombinasi dengan Ekstrak Clinacanthus Nutans terhadap Sel Kanser Payudara Manusia MDA-MB-231) Nur HASNIEzA MOHD rOSlI, CHAN KOK MENg, FArIzA JulIANA NOrDIN, lEONg lEK MuN, Nur SyAzwANI ABDul AzIz & NOr FADIlAH rAJAB ABSTrACT Clinacanthus nutans (C. nutans) leaf extracts have been widely used by cancer patients in Malaysia and local practice claims a cure to cancer. There were several studies done to determine the cytotoxicity potency of C. nutans extracts on various types of cells. However, there is still lacking on the knowledge regarding the combination effect of C. nutans with anticancer drugs. Thus, the study was carried out to determine the cytotoxicity potency of C. nutans extracts and paclitaxel (PTX) alone and, in combination on MDA-MB-231 cells. The cells were treated with 100% ethanol extract of C. nutans (CNE) and water extract of C. nutans (CNA), PTX and combination of both extracts and PTX for 72 hours and the cytotoxic activity was determined using SRB assay. Result showed that CNE had little cytotoxic activity, whereas CNA showed no cytotoxic activity on MDA-MB-231 cells. For combination treatment of C. nutans extracts and PTX, only CNE showed signifcant enhanced PTX-induced cytotoxicity (p < 0.05), meanwhile CNA inhibited PTX-induced cytotoxicity signifcantly (p < 0.05). As a conclusion, CNE was able to increase PTX potency to inhibit the viability of MDA-MB-231 cells. Keywords: Clinacanthus nutans; paclitaxel; MDA-MB-231 cells; cytotoxicity activity ABSTrAK Ekstrak daun Clinacanthus nutans (C. nutans) telah digunakan secara meluas oleh pesakit kanser di Malaysia dan pengamal tempatan mendakwa ia dapat mengubati kanser. Beberapa kajian lepas telah dijalankan untuk menentukan potensi sitotoksisiti ekstrak C. nutans terhadap pelbagai jenis sel. Walau bagaimanapun, pengetahuan mengenai kesan kombinasi C. nutans dengan dadah antikanser adalah masih kurang. Oleh itu, kajian ini telah dijalankan untuk menentukan kesan potensi sitotoksisiti ekstrak C. nutans, paclitaxel (PTX) dan kombinasi di antara ekstrak C. nutans dengan PTX ke atas sel MDA-MB-231. Sel MDA-MB-231 telah dirawat dengan ekstrak 100% etanol C. nutans (CNE) dan esktrak air C. nutans (CNA), PTX dan kombinasi kedua-dua ekstrak dan PTX selama 72 jam dan aktiviti sitotoksik telah ditentukan menggunakan asai SRB. Hasil kajian menunjukkan CNE mempunyai aktiviti sitotoksik yang sedikit, manakala CNA tidak mempunyai aktiviti sitotoksik. Bagi rawatan kombinasi ekstrak C. nutans dan PTX, kombinasi CNE dan PTX menunjukkan peningkatan kesan sitotoksik secara signifkan (p < 0.05). Kesimpulannya, CNE berkebolehan untuk meningkatkan potensi PTX untuk merencat viabiliti sel MDA-MB-231. Kata kunci: Clinacanthus nutans; paclitaxel; sel MDA-MB-231; aktiviti sitotoksisiti INTrODuCTION Breast cancer is the commonest cancer among women (Omar & Tamim 2011). It is estimated that age-standardized rate (ASr) for breast cancer in Malaysia was 38.7 per 100000 with 5410 new cases in 2012, according to IArC (glOBOCAN) in 2012 (IArC 2016). Breast cancers are heterogenous in nature consisting of a few major subtypes including luminal A, luminal B, human epidermal growth factor receptor (HEr-2) positive and basal cell-like (BCl) or triple negative breast cancer (TNBC) (griffiths & Olin 2012; Schnitt 2010; Spitale et al. 2009). Current chemotherapeutic approach includes specific antihormonal therapies that are ready for use against the hormonal receptors such as estrogen receptor (Er) and progesterone receptor (Pr) along with human HEr-2 (griffiths & Olin 2012). For metastatic HEr-2 positive cancer patients, trastuzumab is suggested as first-line treatment which can be administered as a single agent or in combination with endocrine treatment or chemotherapy, including in adjuvant setting (Awada et al. 2012). For TNBC, the only choice of treatment for TNBC is conventional systemic cytotoxic chemotherapy such as taxanes and anthracyclines. Furthermore, TNBC is characterized as higher aggressive behavior, earlier relapses, different patterns or metastases and greater rates of mortality compared to other breast tumors, thus very potent treatment is required (Elias 2010; griffiths & Olin 2012). PTX, a class of taxane drugs is a natural diterpenoid pseudoalkaloid that target microtubules. It interrupts the Chap 14.indd 95 31/05/2018 15:29:59