Luteolin inhibits proliferation, triggers apoptosis and modulates Akt/mTOR and MAP kinase pathways in HeLa cells

Ritu Raina1, Sreepoorna Pramodh2, Naushad Rais1

  • 1School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.

Oncology Letters
|February 12, 2021
PubMed

Insights

Luteolin, a flavonoid, effectively combats cervical cancer cells by inducing apoptosis and inhibiting proliferation. This study confirms its anti-cancer properties through various molecular and cellular assays, highlighting its therapeutic potential.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Flavonoids, a subclass of polyphenols, exhibit anti-cancer effects by reducing cell proliferation and promoting apoptosis.
  • Luteolin is a flavonoid with potential anti-carcinogenic properties that warrant further investigation.

Purpose of the Study:

  • To evaluate the anti-carcinogenic effects of luteolin on HeLa human cervical cancer cells.
  • To elucidate the molecular mechanisms underlying luteolin's action, including apoptosis induction and cell cycle regulation.

Main Methods:

  • Cell viability assay, DNA fragmentation assay, and mitochondrial membrane potential assay.
  • Cell cycle analysis via Annexin/PI staining and flow cytometry.
  • Gene expression analysis and protein profiling array to assess key molecular pathways.

Main Results:

  • Luteolin demonstrated dose- and time-dependent cytotoxicity against HeLa cells, leading to cell cycle arrest in sub-G1 phase.
  • Apoptosis was induced through mitochondrial membrane potential depolarization and DNA fragmentation, with altered expression of pro- and anti-apoptotic genes (e.g., increased BAX, decreased BCL-2).
  • Luteolin modulated cell cycle regulatory genes and key proteins in apoptosis and survival pathways (e.g., AKT, MAPK), indicating inhibition of AKT and MAPK signaling.

Conclusions:

  • Luteolin exhibits significant anti-proliferative and apoptosis-inducing properties against human cervical cancer cells.
  • The anti-cancer effects of luteolin are mediated by the modulation of apoptosis-related genes and proteins and the inhibition of AKT and MAPK signaling pathways.
  • Luteolin shows promise as a potential therapeutic agent for cervical cancer.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.9K