###### Abstract  
Kaempfer, a flavonoidoid, contains a plethora of therapeutic properties and has demonstrated its efficacy against cancer. This study aims to unravel the molecular targets that are being modulated by kaempfer on HeLa cells. Various assays were performed, namely: MTT assay, flow cytometry to analyze DNA content and quantitatte apoptosis. Quantitative PCR and protein profiling were performed to evaluate the modulated manifestation of different genes involved in apoptosis, cell growth and inflammation. Kaempfer exhibited reduction in cell viability of HeLa cells (IC\({}_{50}=50\) uM 48 h), whereas it did not show any significant effect on viability of the AC-16 cell line. Kaempfer-impact apoptosis was definitive, as it different genes that consequently lead to inhibition of cell proliferation, resulting in cell cycle arrest and apoptosis, alleviated inflammation, etc. [3,4]. Polyphenols such as luteolin, chrysin, EGCG (Epigallatocatechin gallate) and quercetin have been reported to modulate PI3K/AKT/mTOR, MAPK/ P38, and WNT pathways and eventually deter cancer growth by halting cell cycle and induce cytotoxicity and apoptosis of the transformed cells [5, 6, 7]. Apoptosis is an intentional cell death mechanism which maintains homeostasis and is regulated by multiple signalling pathways. Cancer cells can escape cell death by progressing through cell cycle checkpoints and unregulated expression of pro-apoptotic and anti-apoptotic protein [8, 9, 10]. Apoptosis is mediated by two core pathways, the death receptor and the mitochondrial-mediated pathways. They congregate at the execution pathway that involves cleavage of caspase-3, which subsequently leads to nuclear fragmentation, and apoptotic body formation that eventually gets phagocytosed [11]. Polyphenols act as a novel therapeutic approach that induces apoptosis of transformed cells through activating pro-apoptotic proteins (BAD, BAX, BID, etc.) or repressing anti-apoptotic proteins (Bcl-2, Bcl-w)/ apoptotic inhibitors (IAFs) [11, 12, 13]. Polyphenols like EGCG, resveratrol and curcumin inhibit cell proliferation by downregulating IGF and Bcl-2 (anti-apoptotic) expression and upregulating the expression of Bax and bad (pro-apoptotic) proteins, etc. [9, 14, 15, 16]. EGCG, resveratrol, curcumin, genistein, quercetin can also induce apoptosis by enhancing ROS and p53 expression in colon cancer [9, 17]. Kaempfer (3,5,7-trihydroxy-2-[4-hydroxyphenyl]-4\(H\)-1-benzopyran-4-one) is a flavonoid ubiquitously present in tea, cabbage, kale, strawberry, grapes, and tomatoes. Kaempfer exerts its anticancer effect by averting cell growth, arresting cell cycle, inducing apoptosis and attenuating oxidative stress and inflammation [18, 19, 20, 21]. Studies have established that kaempfer shows cytotoxicity against HeLa cells and reduces their viability in a dose-dependent manner by downregulating PI3K/AKT and hTERT pathways [22, 23], while it reduces viability of SiHa cells in both dose and time point mode and induces apoptosis by disrupting mitochondrial membrane potential [13]. Likewise, in breast cancer (MCF-7) cells, 25 \(\upmu\)M of Kaempfer treatment suppresses metastasis, i.e., epithelial to mesenchymal transition by downregulating the expression E- and N- Cadherine, Slug, Snails, and MMPs (MMP2-9) [24]. [PERSON] et al. have reported that kaempfer can effectively reduce proliferation of TNBC (triple-negative BC), MDA-MB-231 cells by inhibiting G2/M transition and DNA damage by upregulate cleaved caspase-3, -9 and YH2 AX compared to the control group [12]. Furthermore, the remarkable anti-inflammatory property of kaempfer was established both in vitro and in vivo conditions. Kaempfer inhibits the enzymes of iNOS and COX2, which consequently reduces the ROS level. In addition, it exhibits its protective effect by upregulating anti-oxidative enzymes that can scavenge the free radicals to reduce inflammation [18, 19, 25, 26].