Anti-Tumor Action, Clinical Biochemistry Profile and Phytochemical Constituents of a Pharmacologically Active Fraction of S. crispus in NMU-Induced Rat Mammary Tumour Model

Abstract

Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3) using N-methyl-N-Nitrosourea (NMU)-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.

Formulation of Ethyl Cellulose Microparticles Incorporated Pheophytin A Isolated from Suaeda vermiculata for Antioxidant and Cytotoxic Activities

“…The methyl ester peak appeared as a quartet carbon at δ C 53 ppm with three protons resonating at δ H 3.89 ppm; this peak was similar to that for the pheophytin-a methyl ester reported in the literature [24]. Phytyl ester moiety has been identified and compared to the data published for pheophytin a [24,25]. According to spectral data, in addition to literature, pheo-a has been isolated for the first time from S. vermiculata (Figure 1).…”

Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

“…Generally, it has been reported that treatment with mixtures of PS (mainly b-sitosterol, campesterol and stigmasterol) from different plant extracts showed no antiproliferative effects upon MCF-7 cells at concentrations of 0.1-100 mg/ml and incubation times of 24, 48 and 72 h (Malek et al 2009;Rahman et al 2013;Yaacob et al 2015). Unlike, the PS-ingredient used in our study, mainly comprising b-sitosterol, showed an antiproliferative effect (17 and 53% at 24 and 48 h, respectively) at the lowest concentration used (5.39 mg/ml, 13 mM).…”

“…The antiproliferative activity of b-sitosterol standards has been studied in breast cancer (MCF-7) (Awad et al 2007(Awad et al , 2008Rubis et al 2010), colon cancer (HT-29, Caco-2 and/or HCT116) (Awad et al 1996(Awad et al , 1998Choi et al 2003;Daly et al 2009;Montserrat-de la Paz et al 2015) and cervical cancer (HeLa) cells (Cheng et al 2015). Likewise, the anticarcinogenic effects of isolated PS from plant extracts have also been evaluated in MCF-7 (Chai et al 2008;Malek et al 2009;Rahman et al 2013;Yaacob et al 2015;Tahsin et al 2017), in HCT116 (Malek et al 2009;Rahman et al 2013) and in HeLa cells (Block et al 2004;Csupor-Loffler et al 2011;Hamdan et al 2011;Han et al 2013).…”

Uncoupling genotoxic stress responses from circadian control increases susceptibility to mammary carcinogenesis

“…By contrast, feral rats and the Copenhagen (COP) and Wistar-Kyoto strains are highly resistant [37]. A single carcinogenic dose of NMU induces mammary carcinogenesis in female rats from different strains including Wistar [38], F344 [39], Lewis [40] and Sprague Dawley [41, 42], and circadian rhythms have been studied in all these strains [39, 43–45]. Susceptible strains vary in their sensitivities to chemicals, hormones and radiation, and are known to have differences in the circadian rhythms of circulating hormones and inflammatory cells [37, 45].…”