Vapor of Volatile Oils from Litsea cubeba Seed Induces Apoptosis and Causes Cell Cycle Arrest in Lung Cancer Cells

Abstract

Non-small cell lung carcinoma (NSCLC) is a major killer in cancer related human death. Its therapeutic intervention requires superior efficient molecule(s) as it often becomes resistant to present chemotherapy options. Here we report that vapor of volatile oil compounds obtained from Litsea cubeba seeds killed human NSCLC cells, A549, through the induction of apoptosis and cell cycle arrest. Vapor generated from the combined oils (VCO) deactivated Akt, a key player in cancer cell survival and proliferation. Interestingly VCO dephosphorylated Akt at both Ser473 and Thr308; through the suppression of mTOR and pPDK1 respectively. As a consequence of this, diminished phosphorylation of Bad occurred along with the decreased Bcl-xL expression. This subsequently enhanced Bax levels permitting the release of mitochondrial cytochrome c into the cytosol which concomitantly activated caspase 9 and caspase 3 resulting apoptotic cell death. Impairment of Akt activation by VCO also deactivated Mdm2 that effected overexpression of p53 which in turn upregulated p21 expression. This causes enhanced p21 binding to cyclin D1 that halted G1 to S phase progression. Taken together, VCO produces two prong effects on lung cancer cells, it induces apoptosis and blocked cancer cell proliferation, both occurred due to the deactivation of Akt. In addition, it has another crucial advantage: VCO could be directly delivered to lung cancer tissue through inhalation.

Inhibitory Effect of Herbal Remedy PERVIVO and Anti-Inflammatory Drug Sulindac on L-1 Sarcoma Tumor Growth and Tumor Angiogenesis in Balb/c Mice

“…One report described antiproliferative activity of Gentiana triflora root extract on cultured and implanted tumor cells [29]. Fruit oils of Litsea cubeba from Taiwan exhibited cytotoxic activity against human lung, liver, and oral cancer cells in vitro [30, 31]. Galangin, flavonol present in Alpinia galanga rhizome, induced apoptosis of cancer cells [32, 33].…”

Comprehensive Analysis of the Chemical Composition and In Vitro Cytotoxic Mechanisms of Pallines Spinosa Flower and Leaf Essential Oils Against Breast Cancer Cells

“…Several plant essential oils have been documented to arrest cell cycle leading to tumor cell death [35, 36]. When MCF-7 and MDA-MB-231 cells were treated with increasing concentrations of F-PSEO and L-PSEO for 24 h, a dose dependent cell cycle arrest at G0/G1 phase was evident with concomitant decrease in the S and G2/M phases (Fig.…”

A New Diterpene from Litsea cubeba Fruits: Structure Elucidation and Capability to Induce Apoptosis in HeLa Cells

“…This datum indicated the existence of a [C=C (13) H-C (4) H 2 -C (8) H-] fragment. In addition, two vinyl methine protons at δ 6.54 and δ 6.88 (1H, d, J = 15.12 Hz), and two methine protons at δ 5.87 and δ 6.83 (1H, d, J = 5.52 Hz) were also correlated to be a [-C (12) H=C (17) H-] fragment, and a [C=C (11) H-C (16) H=C] fragment, respectively. The chemical structure of cubelin ( Figure 1) was constructed based on the long ranged protoncarbon correlations as displayed in the HMBC spectrum ( Figure 2A).…”

“…The major chemical constituent of this oil is citral, which comprises geranial (E-citral) and neral (Z-citral) [3][4][5][6]. The oil has been found to have bio-activities such as anti-inflammatory, antioxidant, pesticidal, antimicrobial, anticancer and neuropharmacological properties [7][8][9][10][11][12]. However, past research on biological active substances in L. cubeba fruits have mainly focused on the essential oil, while the possible existence of beneficial non-essential oil compounds has not been explored.…”

“…These data clearly supported the partial structure B (Figure 1). For the fragment containing the [C=C (11) H-C (16) H=C] unit, cross-peaks between H-16 and C-9, C-18, C-19, and between H-19 and C-9, C-15, as well as between H-11 and C-15 suggested a connection between C-19 and C-15. Therefore, C-15 should be connected to C-16 and C-9.…”